Diabetes mellitus is a systemic disease characterized by disorders in the metabolism of insulin, carbohydrates, fats, and proteins, and in the structure and function of blood vessels. There are several causes of the disease including a large genetic component as well as a relationship to the type and amount of physical exercise and diet of the individual. The primary symptom of acute diabetes mellitus is hyperglycemia, often accompanied by glucosuria, the presence in urine of abnormal amounts of glucose, and polyuria, the excretion of large volumes of urine. Additional symptoms arise in chronic or long-standing diabetes. These include degeneration of the walls of blood vessels. Although many different organs are affected by these vascular changes, the eyes appear to be the most susceptible. As such, long-standing diabetes mellitus, even when treated with insulin, is a leading cause of blindness.
There are two recognized types of diabetes. Juvenile onset, or ketosis-prone, diabetes develops early in life with much more severe symptoms, and has a near-certain prospect of later vascular involvement. Control of this type of diabetes is often difficult. The second type of diabetes is adult onset, or ketosis-resistant, diabetes. This form develops later in life, is milder and has a more gradual onset.
One of the most significant advancements in the history of medical science came in 1922 when Banting and Best demonstrated the therapeutic affects of insulin in diabetic humans. However, even today, a clear picture of the basic biochemical defects of the disease is not known, and diabetes is still a serious health problem. It is believed that two percent or more of the population of the United States is afflicted with some form of diabetes.
The introduction of orally effective hypoglycemic agents was also an important development in the treatment of diabetes mellitus. Hypoglycemic agents are useful in the treatment of hyperglycemia by lowering blood glucose levels. The term "hyperglycemia" refers to a clinical condition resulting from an abnormally high blood glucose level. Oral hypoglycemic agents are normally used in the treatment of adult onset diabetes since older individuals have a better chance of recovery than an individual afflicted with juvenile onset diabetes.
The present invention relates to a new class of orally active hypoglycemic agents capable of lowering blood glucose levels in mammals with adult onset diabetes.